It has been speculated that the veterinary use of ceftiofur in food animals has resulted in the emergence of third generation cephalosporin resistant pathogens that threaten the public health. However, evidence linking ceftiofur use in animals to the emergence and dissemination of third generation cephalosporin resistant bacteria is largely circumstantial, relying on limited isolations of resistant bacteria from food animals and meat products. Our long-term goal is to reduce the risk of zoonotic transfer of third generation cephalosporin resistant food-borne pathogens. Our immediate goal is to fill critical information gaps necessary to assess the public health risk attributable to ceftiofur use in food animals. Our central hypothesis, based on our preliminary observations, is that ceftiofur use in swine and cattle selects for the emergence and rapid dissemination of third generation cephalosporin resistant enteric bacteria. This then results in the increased risk of food-borne zoonotic transfer through contamination of meat products during harvest and processing. We will test our central hypothesis and accomplish the overall objective of this research by answering 3 specific aims: 1. Establish the prevalence of third generation cephalosporin resistance throughout the food chain 2. Track third generation cephalosporin resistant organisms through the food chain 3. Determine the impact of ceftiofur use restriction on prevalence of third generation cephalosporin resistance. These results will establish the association between the use of ceftiofur in food animals and the emergence and dissemination of third generation cephalosporin bacteria throughout the food supply to the consumer. This will have significant positive effects on the reduction of antimicrobial resistant pathogens, because it will provide scientifically based information targeted at the primary decision makers regarding ceftiofur use.